DOCSLIB.ORG

Anticancer Effects of Β-Elemene in Gastric Cancer Cells and Its Potential Underlying Proteins: a Proteomic Study

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Anticancer Effects of Β-Elemene in Gastric Cancer Cells and Its Potential Underlying Proteins: a Proteomic Study ONCOLOGY REPORTS 32: 2635-2647, 2014 Anticancer effects of β-elemene in gastric cancer cells and its potential underlying proteins: A proteomic study JUN-SONG LIU, SHI-CAI HE, ZHENG-LIANG ZHANG, RUI CHEN, LIN FAN, GUANG-LIN QIU, SHUAI CHANG, LIANG LI and XIANG-MING CHE Department of General Surgery, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China Received July 4, 2014; Accepted August 26, 2014 DOI: 10.3892/or.2014.3490 Abstract. Gastric cancer is a common malignancy with a Introduction poor prognosis. β-elemene is a broad-spectrum anticancer drug extracted from the traditional Chinese medicinal herb Gastric cancer is the fourth most common malignancy in Curcuma wenyujin. In the present study, we investigated the the world and the second leading cause of cancer-related anticancer effects of β-elemene in gastric cancer cells and the mortality (1). At present, surgical resection remains the potential proteins involved. Human SGC7901 and MKN45 main therapeutic strategy for gastric cancer, supplemented gastric cancer cells were treated with different concentrations with perioperative chemotherapy, chemoradiotherapy and/or of β-elemene. Cell viability, clonogenic survival and apoptotic immunotherapy (2-5). However, most patients are diagnosed cell death were assessed. β-elemene inhibited viability and with advanced gastric cancer which may have progressed decreased clonogenic survival of gastric cancer cells in a beyond the curative potential of surgical operation (6,7). In dose-dependent manner. Apoptosis induction contributed to addition, previous studies have demonstrated that a consid- the anticancer effects. We then employed a proteomic method, erable proportion of patients receiving potentially curative isobaric tags for relative and absolute quantitation (iTRAQ), to resection experienced recurrences which lead to unfavorable detect the proteins altered by β-elemene. In total, 147 upregu- prognosis (8,9). Adjuvant therapy, such as chemotherapy, lated proteins and 86 downregulated proteins were identified provides rather limited survival advantage (10,11). These facts in response to β-elemene treatment in SGC7901 gastric cancer attest to the deficiency in the current strategies for treating cells. Among them, expression of p21-activated protein gastric cancer and the demand for novel approaches to the kinase-interacting protein 1 (PAK1IP1), Bcl-2-associated tran- management of gastric cancer. scription factor 1 (BTF) and topoisomerase 2-α (TOPIIα) were Among various ingredients eligible for adjuvant therapy validated by western blot analyses and the trends were consis- for gastric cancer, the significance of natural products, tent with iTRAQ results. Top pathways involved in β-elemene particularly the essence extracted from Chinese herbs are treatment in SGC7901 gastric cancer cells included ribo- gaining increasing attention in basic and clinical research (12). some signaling, peroxisome proliferator-activated receptors β-elemene (1-methyl-1-vinyl-2,4-diisopropenyl-cyclohexane) (PPARs) signaling pathway, regulation of actin cytoskeleton, is a novel anticancer agent extracted from the Chinese medicinal phagosome, biosynthesis and metabolism of some amino acids. herb Curcuma wenyujin (13). In recent studies, β-elemene was Collectively, our results suggest a promising therapeutic role shown to have diverse anticancer potential, such as inhibiting of β-elemene in gastric cancer. The differentially expressed proliferation and inducing apoptosis of cancer cells, and inter- proteins provide further insight into the potential mechanisms acting with multiple oncogenic or tumor suppressing signaling involved in gastric cancer treatment using β-elemene. pathways in a broad spectrum of cancers (14-16). Other studies found that β-elemene could enhance tumor chemosensitivity or overcome drug resistance (17,18). In addition, β-elemene has been approved by the China Food and Drug Administration as a therapeutic drug in clinical practice where its efficacy has been exhibited when combined with first‑line chemotherapy Correspondence to: Professor Xiang-Ming Che, Department of for malignant tumors (19,20). However, the mechanisms by General Surgery, The First Affiliated Hospital of Medical College of which β-elemene is involved in tumor suppressing activities Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China remain largely unknown. E-mail: [email protected] In the present study, we examined the anticancer potential of β-elemene in the proliferation, clonogenic survival and Key words: β-elemene, gastric cancer, proliferation, apoptosis, apoptosis in SGC7901 and MKN45 gastric cancer cells. Then, proteomics in order to investigate the molecules through which β-elemene exhibited its anticancer effects and to obtain a better under- standing of its therapeutic role in gastric cancer, we employed 2636 LIU et al: proteomic analysis of anticancer effects of β-elemene in gastric cancer cells isobaric tags for relative and absolute quantitation (iTRAQ), a number of cells seeding x PE). This assay was carried out in high‑throughput proteomic approach, to profile proteins that duplicate. were differentially expressed following β-elemene treatment in gastric cancer cells. Protein preparation. After SGC7901 cells were treated with or without β-elemene at 30 µg/ml for 48 h, cell total protein Materials and methods was extracted. Protein concentration was determined using Pierce™ BCA Protein Assay (Thermo Scientific, Rockford, Reagents. β-elemene was obtained from Jingang Pharma- IL, USA). Total protein extracted from two separate experi- ceutical Co. (Dalian, China). Annexin V-FITC/PI apoptosis ments was mixed together for use in the subsequent proteomic detection kit was purchased from 7 Sea Pharmacy Technology analysis. Protein samples were reduced and alkylated, then (Shanghai, China). iTRAQ reagents were from Applied added into 5‑fold volume of ice‑cold acetone and put in ‑20˚C Biosystems (New York, NY, USA). Anti-PAK1IP1 antibody condition overnight. Then, the precipitate was harvested by was purchased from Abcam (#ab67348; UK). Anti-TOPIIα centrifugation at 25,000 x g at 4˚C for 20 min and dried in the antibody was obtained from Proteintech (#20233-1-AP; USA). air for 5 min. The precipitate was dissolved in 200 µl 0.5 M Anti-BTF antibody was from BD Biosciences Pharmingen tetraethylammonium bromide (TEAB) and dealt with sonicate (#611726; San Diego, CA, USA). for 15 min. Finally, the supernatant was harvested and quanti- fied. Cell culture. The SGC7901 and MKN45 human gastric cancer cell lines were obtained from the Lab Animal Centre of the iTRAQ proteomic analysis. One hundred micrograms of protein Fourth Military Medical University (Xi'an, China). Cells were were taken out from each sample and digested with trypsin. cultured in RPMI-1640 medium (HyClone, USA), supple- Thereafter, the peptides of each sample were labeled with mented with 10% fetal bovine serum (Sijiqing, Huzhou City, iTRAQ reagents respectively, according to the manufacturer's China) at 37˚C with 5% CO2 in a humidified atmosphere. protocol (Applied Biosystems) (SGC7901-control-114 tag and SGC7901-β-elemene treated-115 tag). Then, the labeled MTT assay. Cell viability was measured using 3-(4,5-dimethyl- samples were pooled and sent to fractionating using strong thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. cation exchange (SCX) chromatography (Shimadzu LC-20AB The cells were seeded in 24-well plates at 5-10x104/well. After HPLC Pump system and the 4.6x250 mm Ultremex SCX overnight incubation, cells were exposed to different concen- column). After elution, 20 fractions of peptides were obtained. trations of β-elemene for 24-72 h. Then, 50 µl MTT (5 mg/ml) Each fraction was then desalted by Strata-X C18 column was added to each well and the cells were incubated for another (Phenomenex) and vacuum-dried. Each fraction of peptides 4 h at 37˚C. After gentle removal of the supernatant, 500 µl was resuspended in buffer A (5% ACN, 0.1% FA) and dimethyl sulfoxide (DMSO) was added to each well to solu- centrifuged at 20,000 x g for 10 min to remove the insoluble bilize the purple formazan crystal. The optical density (OD) substances. In each fraction, the final concentration of peptides was measured using a microplate reader at 490 nm and then was ~0.5 µg/µl. Five microlitres (~2.5 µg) of supernatant transformed into cell viability using the following formula: was loaded onto a Shimadzu LC-20AD nano HPLC by the Cell viability = (OD of the experimental sample)/(OD of the autosampler for separation. Mass spectrometric analysis of the control sample) x 100%. iTRAQ labelled peptides was performed using a Q Exactive (Thermo Fisher Scientific, San Jose, CA, USA) coupled online Annexin V-FITC/PI apoptosis detection assay. To explore the to the HPLC. Data processing of LC-MS/MS samples was effect of β-elemene on apoptotic cell death, Annexin V-FITC/PI searched against the International Protein Index (IPI) human apoptosis detection assay was used. The cells were seeded in protein database version 3.87 FASTA (91,464 sequences) using 6-well plates at 3x105/well. After overnight incubation, cells Mascot 2.3.02 software (Matrix Science, UK). When the fold- were exposed to different concentrations of β-elemene for change of protein abundance was >1.2 and the P-value was 24 h. Then, cells were collected and manipulated following the <0.05, we defined this protein as differentially expressed. The manufacturer's instructions, incubated with Annexin V-FITC identified proteins were categorized according to the Gene and propidium iodide (PI), then analyzed using flow cytometry Ontology (GO) classification terms (http://www.geneontology. (FCM; BD Biosciences-Clontech, Palo Alto, CA, USA) within org/). GO enrichment analysis was performed to display the 30 min. GO terms which the differentially expressed proteins enriched in all identified proteins. Clonogenic survival assay. Cells were trypsinized and counted. Then, 200 cells were seeded into each well of Western blot analyses. Equal amounts of protein samples 6-well plates. After overnight incubation for attachment and were subjected to SDS-PAGE.
Load more

Recommended publications
  • The Rise and Fall of the Bovine Corpus Luteum
    University of Nebraska Medical Center DigitalCommons@UNMC Theses & Dissertations Graduate Studies Spring 5-6-2017 The Rise and Fall of the Bovine Corpus Luteum Heather Talbott University of Nebraska Medical Center Follow this and additional works at: https://digitalcommons.unmc.edu/etd Part of the Biochemistry Commons, Molecular Biology Commons, and the Obstetrics and Gynecology Commons Recommended Citation Talbott, Heather, "The Rise and Fall of the Bovine Corpus Luteum" (2017). Theses & Dissertations. 207. https://digitalcommons.unmc.edu/etd/207 This Dissertation is brought to you for free and open access by the Graduate Studies at DigitalCommons@UNMC. It has been accepted for inclusion in Theses & Dissertations by an authorized administrator of DigitalCommons@UNMC. For more information, please contact [email protected]. THE RISE AND FALL OF THE BOVINE CORPUS LUTEUM by Heather Talbott A DISSERTATION Presented to the Faculty of the University of Nebraska Graduate College in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Biochemistry and Molecular Biology Graduate Program Under the Supervision of Professor John S. Davis University of Nebraska Medical Center Omaha, Nebraska May, 2017 Supervisory Committee: Carol A. Casey, Ph.D. Andrea S. Cupp, Ph.D. Parmender P. Mehta, Ph.D. Justin L. Mott, Ph.D. i ACKNOWLEDGEMENTS This dissertation was supported by the Agriculture and Food Research Initiative from the USDA National Institute of Food and Agriculture (NIFA) Pre-doctoral award; University of Nebraska Medical Center Graduate Student Assistantship; University of Nebraska Medical Center Exceptional Incoming Graduate Student Award; the VA Nebraska-Western Iowa Health Care System Department of Veterans Affairs; and The Olson Center for Women’s Health, Department of Obstetrics and Gynecology, Nebraska Medical Center.
    [Show full text]
  • Allele-Specific Expression of Ribosomal Protein Genes in Interspecific Hybrid Catfish
    Allele-specific Expression of Ribosomal Protein Genes in Interspecific Hybrid Catfish by Ailu Chen A dissertation submitted to the Graduate Faculty of Auburn University in partial fulfillment of the requirements for the Degree of Doctor of Philosophy Auburn, Alabama August 1, 2015 Keywords: catfish, interspecific hybrids, allele-specific expression, ribosomal protein Copyright 2015 by Ailu Chen Approved by Zhanjiang Liu, Chair, Professor, School of Fisheries, Aquaculture and Aquatic Sciences Nannan Liu, Professor, Entomology and Plant Pathology Eric Peatman, Associate Professor, School of Fisheries, Aquaculture and Aquatic Sciences Aaron M. Rashotte, Associate Professor, Biological Sciences Abstract Interspecific hybridization results in a vast reservoir of allelic variations, which may potentially contribute to phenotypical enhancement in the hybrids. Whether the allelic variations are related to the downstream phenotypic differences of interspecific hybrid is still an open question. The recently developed genome-wide allele-specific approaches that harness high- throughput sequencing technology allow direct quantification of allelic variations and gene expression patterns. In this work, I investigated allele-specific expression (ASE) pattern using RNA-Seq datasets generated from interspecific catfish hybrids. The objective of the study is to determine the ASE genes and pathways in which they are involved. Specifically, my study investigated ASE-SNPs, ASE-genes, parent-of-origins of ASE allele and how ASE would possibly contribute to heterosis. My data showed that ASE was operating in the interspecific catfish system. Of the 66,251 and 177,841 SNPs identified from the datasets of the liver and gill, 5,420 (8.2%) and 13,390 (7.5%) SNPs were identified as significant ASE-SNPs, respectively.
    [Show full text]
  • Repositório Da Universidade De Lisboa
    UNIVERSIDADE DE LISBOA FACULDADE DE CIÊNCIAS DEPARTAMENTO DE BIOLOGIA ANIMAL TOWARDS THE IDENTIFICATION OF BIOMARKERS FOR CYSTIC FIBROSIS BY PROTEOMICS NUNO MIGUEL ANTUNES GARCIA CHARRO DOUTORAMENTO EM BIOLOGIA ESPECIALIDADE BIOLOGIA MOLECULAR 2011 ii iii iv UNIVERSIDADE DE LISBOA FACULDADE DE CIÊNCIAS DEPARTAMENTO DE BIOLOGIA ANIMAL TOWARDS THE IDENTIFICATION OF BIOMARKERS FOR CYSTIC FIBROSIS BY PROTEOMICS Tese orientada pela Doutora Deborah Penque e Professora Doutora Ana Maria Viegas Gonçalves Crespo NUNO MIGUEL ANTUNES GARCIA CHARRO DOUTORAMENTO EM BIOLOGIA (BIOLOGIA MOLECULAR) 2011 v The research described in this thesis was conducted at Laboratório de Proteómica, Departamento de Genética, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA, I.P.), Lisbon, Portugal; Clinical Proteomics Facility, University of Pittsburgh Medical Centre, Pennsylvania, USA; and Laboratory of Proteomics and Analytical Technologies, National Cancer Institute at Frederick, Maryland, USA. Work partially supported by Fundação para a Ciência e a Tecnologia (FCT), Fundo Europeu para o Desenvolvimento (FEDER) (POCI/SAU-MMO/56163/2004), FCT/Poly-Annual Funding Program and FEDER/Saúde XXI Program (Portugal). Nuno Charro is a recipient of FCT doctoral fellowship (SFRH/BD/27906/2006). vi Agradecimentos/Acknowledgements “Nothing is hidden that will not be made known; Nothing is secret that will not come to light” Desde muito pequeno, a minha vontade em querer saber mais e porquê foi sempre presença constante. Ao iniciar e no decorrer da minha (ainda) curta na investigação científica, as perguntas foram mudando, o método também e várias pessoas contribuíram para o crescimento e desenvolvimento da minha personalidade científica e pessoal. Espero não me esquecer de ninguém e, se o fizer, não é intencional; apenas falibilidade.
    [Show full text]
  • Associated 16P11.2 Deletion in Drosophila Melanogaster
    ARTICLE DOI: 10.1038/s41467-018-04882-6 OPEN Pervasive genetic interactions modulate neurodevelopmental defects of the autism- associated 16p11.2 deletion in Drosophila melanogaster Janani Iyer1, Mayanglambam Dhruba Singh1, Matthew Jensen1,2, Payal Patel 1, Lucilla Pizzo1, Emily Huber1, Haley Koerselman3, Alexis T. Weiner 1, Paola Lepanto4, Komal Vadodaria1, Alexis Kubina1, Qingyu Wang 1,2, Abigail Talbert1, Sneha Yennawar1, Jose Badano 4, J. Robert Manak3,5, Melissa M. Rolls1, Arjun Krishnan6,7 & 1234567890():,; Santhosh Girirajan 1,2,8 As opposed to syndromic CNVs caused by single genes, extensive phenotypic heterogeneity in variably-expressive CNVs complicates disease gene discovery and functional evaluation. Here, we propose a complex interaction model for pathogenicity of the autism-associated 16p11.2 deletion, where CNV genes interact with each other in conserved pathways to modulate expression of the phenotype. Using multiple quantitative methods in Drosophila RNAi lines, we identify a range of neurodevelopmental phenotypes for knockdown of indi- vidual 16p11.2 homologs in different tissues. We test 565 pairwise knockdowns in the developing eye, and identify 24 interactions between pairs of 16p11.2 homologs and 46 interactions between 16p11.2 homologs and neurodevelopmental genes that suppress or enhance cell proliferation phenotypes compared to one-hit knockdowns. These interac- tions within cell proliferation pathways are also enriched in a human brain-specific network, providing translational relevance in humans. Our study indicates a role for pervasive genetic interactions within CNVs towards cellular and developmental phenotypes. 1 Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA. 2 Bioinformatics and Genomics Program, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA.
    [Show full text]
  • Cyclin-Dependent Kinase 2 (Cdk2) Controls Phosphatase-Regulated Signaling and Function in Platelets
    bioRxiv preprint doi: https://doi.org/10.1101/2020.05.31.126953; this version posted June 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Cyclin-dependent kinase 2 (Cdk2) controls phosphatase-regulated signaling and function in platelets Paul R. Woods, Jr.,1,2 Brian L. Hood5, Sruti Shiva,$4 Thomas P. Conrads5, Sarah Suchko,2 Richard Steinman, 1,2,4# Departments oF Medicine1, Hillman Cancer Center2, Vascular Medicine Institute3, Department oF Molecular Pharmacology and Chemical Biology4, University of Pittsburgh School of Medicine; The Henry M. Jackson Foundation For the Advancement of Military Medicine, Inc., Inova Women’s Service Line, Inova Health System5 #Corresponding author: Richard Steinman, MD, PhD Associate Professor of Medicine and Pharmacology Associate Dean, Director Medical Scientist Training Program Director, Physician Scientist Training Program University of Pittsburgh School of Medicine 2.26f Hillman Cancer Center 5117 Centre Avenue Pittsburgh, PA 15213 USA phone: 412 6233237 fax: 412 6234840 [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.05.31.126953; this version posted June 28, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract Cell cycle regulatory molecules including cyclin-dependent kinases can be recruited into non-nuclear pathways to coordinate cell cycling with the energetic state oF the cell or with Functions such as motility.
    [Show full text]
  • SHOC2–MRAS–PP1 Complex Positively Regulates RAF Activity and Contributes to Noonan Syndrome Pathogenesis
    SHOC2–MRAS–PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis Lucy C. Younga,1, Nicole Hartiga,2, Isabel Boned del Ríoa, Sibel Saria, Benjamin Ringham-Terrya, Joshua R. Wainwrighta, Greg G. Jonesa, Frank McCormickb,3, and Pablo Rodriguez-Vicianaa,3 aUniversity College London Cancer Institute, University College London, London WC1E 6DD, United Kingdom; and bHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158 Contributed by Frank McCormick, September 18, 2018 (sent for review November 22, 2017; reviewed by Deborah K. Morrison and Marc Therrien) Dephosphorylation of the inhibitory “S259” site on RAF kinases CRAF/RAF1 mutations are also frequently found in NS and (S259 on CRAF, S365 on BRAF) plays a key role in RAF activation. cluster around the S259 14-3-3 binding site, enhancing CRAF ac- The MRAS GTPase, a close relative of RAS oncoproteins, interacts tivity through disruption of 14-3-3 binding (8) and highlighting the with SHOC2 and protein phosphatase 1 (PP1) to form a heterotri- key role of this regulatory step in RAF–ERK pathway activation. meric holoenzyme that dephosphorylates this S259 RAF site. MRAS is a very close relative of the classical RAS oncoproteins MRAS and SHOC2 function as PP1 regulatory subunits providing (H-, N-, and KRAS, hereafter referred to collectively as “RAS”) the complex with striking specificity against RAF. MRAS also func- and shares most regulatory and effector interactions as well as tions as a targeting subunit as membrane localization is required transforming ability (9–11). However, MRAS also has specific for efficient RAF dephosphorylation and ERK pathway regulation functions of its own, and uniquely among RAS family GTPases, it in cells.
    [Show full text]
  • Attachment PDF Icon
    Spectrum Name of Protein Count of Peptides Ratio (POL2RA/IgG control) POLR2A_228kdBand POLR2A DNA-directed RNA polymerase II subunit RPB1 197 NOT IN CONTROL IP POLR2A_228kdBand POLR2B DNA-directed RNA polymerase II subunit RPB2 146 NOT IN CONTROL IP POLR2A_228kdBand RPAP2 Isoform 1 of RNA polymerase II-associated protein 2 24 NOT IN CONTROL IP POLR2A_228kdBand POLR2G DNA-directed RNA polymerase II subunit RPB7 23 NOT IN CONTROL IP POLR2A_228kdBand POLR2H DNA-directed RNA polymerases I, II, and III subunit RPABC3 19 NOT IN CONTROL IP POLR2A_228kdBand POLR2C DNA-directed RNA polymerase II subunit RPB3 17 NOT IN CONTROL IP POLR2A_228kdBand POLR2J RPB11a protein 7 NOT IN CONTROL IP POLR2A_228kdBand POLR2E DNA-directed RNA polymerases I, II, and III subunit RPABC1 8 NOT IN CONTROL IP POLR2A_228kdBand POLR2I DNA-directed RNA polymerase II subunit RPB9 9 NOT IN CONTROL IP POLR2A_228kdBand ALMS1 ALMS1 3 NOT IN CONTROL IP POLR2A_228kdBand POLR2D DNA-directed RNA polymerase II subunit RPB4 6 NOT IN CONTROL IP POLR2A_228kdBand GRINL1A;Gcom1 Isoform 12 of Protein GRINL1A 6 NOT IN CONTROL IP POLR2A_228kdBand RECQL5 Isoform Beta of ATP-dependent DNA helicase Q5 3 NOT IN CONTROL IP POLR2A_228kdBand POLR2L DNA-directed RNA polymerases I, II, and III subunit RPABC5 5 NOT IN CONTROL IP POLR2A_228kdBand KRT6A Keratin, type II cytoskeletal 6A 3 NOT IN CONTROL IP POLR2A_228kdBand POLR2K DNA-directed RNA polymerases I, II, and III subunit RPABC4 2 NOT IN CONTROL IP POLR2A_228kdBand RFC4 Replication factor C subunit 4 1 NOT IN CONTROL IP POLR2A_228kdBand RFC2
    [Show full text]
  • Pig Antibodies
    Pig Antibodies gene_name sku Entry_Name Protein_Names Organism Length Identity CDX‐2 ARP31476_P050 D0V4H7_PIG Caudal type homeobox 2 (Fragment) Sus scrofa (Pig) 147 100.00% CDX‐2 ARP31476_P050 A7MAE3_PIG Caudal type homeobox transcription factor 2 (Fragment) Sus scrofa (Pig) 75 100.00% Tnnt3 ARP51286_P050 Q75NH3_PIG Troponin T fast skeletal muscle type Sus scrofa (Pig) 271 85.00% Tnnt3 ARP51286_P050 Q75NH2_PIG Troponin T fast skeletal muscle type Sus scrofa (Pig) 266 85.00% Tnnt3 ARP51286_P050 Q75NH1_PIG Troponin T fast skeletal muscle type Sus scrofa (Pig) 260 85.00% Tnnt3 ARP51286_P050 Q75NH0_PIG Troponin T fast skeletal muscle type Sus scrofa (Pig) 250 85.00% Tnnt3 ARP51286_P050 Q75NG8_PIG Troponin T fast skeletal muscle type Sus scrofa (Pig) 266 85.00% Tnnt3 ARP51286_P050 Q75NG7_PIG Troponin T fast skeletal muscle type Sus scrofa (Pig) 260 85.00% Tnnt3 ARP51286_P050 Q75NG6_PIG Troponin T fast skeletal muscle type Sus scrofa (Pig) 250 85.00% Tnnt3 ARP51286_P050 TNNT3_PIG Troponin T, fast skeletal muscle (TnTf) Sus scrofa (Pig) 271 85.00% ORF Names:PANDA_000462 EMBL EFB13877.1OrganismAiluropod High mobility group protein B2 (High mobility group protein a melanoleuca (Giant panda) ARP31939_P050 HMGB2_PIG 2) (HMG‐2) Sus scrofa (Pig) 210 100.00% Agpat5 ARP47429_P050 B8XTR3_PIG 1‐acylglycerol‐3‐phosphate O‐acyltransferase 5 Sus scrofa (Pig) 365 85.00% irf9 ARP31200_P050 Q29390_PIG Transcriptional regulator ISGF3 gamma subunit (Fragment) Sus scrofa (Pig) 57 100.00% irf9 ARP31200_P050 Q0GFA1_PIG Interferon regulatory factor 9 Sus scrofa (Pig)
    [Show full text]
  • The VE-Cadherin/Amotl2 Mechanosensory Pathway Suppresses Aortic InAmmation and the Formation of Abdominal Aortic Aneurysms
    The VE-cadherin/AmotL2 mechanosensory pathway suppresses aortic inammation and the formation of abdominal aortic aneurysms Yuanyuan Zhang Karolinska Institute Evelyn Hutterer Karolinska Institute Sara Hultin Karolinska Institute Otto Bergman Karolinska Institute Maria Forteza Karolinska Institute Zorana Andonovic Karolinska Institute Daniel Ketelhuth Karolinska University Hospital, Stockholm, Sweden Joy Roy Karolinska Institute Per Eriksson Karolinska Institute Lars Holmgren ( [email protected] ) Karolinska Institute Article Keywords: arterial endothelial cells (ECs), vascular disease, abdominal aortic aneurysms Posted Date: June 15th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-600069/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License The VE-cadherin/AmotL2 mechanosensory pathway suppresses aortic inflammation and the formation of abdominal aortic aneurysms Yuanyuan Zhang1, Evelyn Hutterer1, Sara Hultin1, Otto Bergman2, Maria J. Forteza2, Zorana Andonovic1, Daniel F.J. Ketelhuth2,3, Joy Roy4, Per Eriksson2 and Lars Holmgren1*. 1Department of Oncology-Pathology, BioClinicum, Karolinska Institutet, Stockholm, Sweden. 2Department of Medicine Solna, BioClinicum, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 3Department of Cardiovascular and Renal Research, Institutet of Molecular Medicine, Univ. of Southern Denmark, Odense, Denmark 4Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm,
    [Show full text]
  • Supplementary Table 2
    Supplementary Table 2. Differentially Expressed Genes following Sham treatment relative to Untreated Controls Fold Change Accession Name Symbol 3 h 12 h NM_013121 CD28 antigen Cd28 12.82 BG665360 FMS-like tyrosine kinase 1 Flt1 9.63 NM_012701 Adrenergic receptor, beta 1 Adrb1 8.24 0.46 U20796 Nuclear receptor subfamily 1, group D, member 2 Nr1d2 7.22 NM_017116 Calpain 2 Capn2 6.41 BE097282 Guanine nucleotide binding protein, alpha 12 Gna12 6.21 NM_053328 Basic helix-loop-helix domain containing, class B2 Bhlhb2 5.79 NM_053831 Guanylate cyclase 2f Gucy2f 5.71 AW251703 Tumor necrosis factor receptor superfamily, member 12a Tnfrsf12a 5.57 NM_021691 Twist homolog 2 (Drosophila) Twist2 5.42 NM_133550 Fc receptor, IgE, low affinity II, alpha polypeptide Fcer2a 4.93 NM_031120 Signal sequence receptor, gamma Ssr3 4.84 NM_053544 Secreted frizzled-related protein 4 Sfrp4 4.73 NM_053910 Pleckstrin homology, Sec7 and coiled/coil domains 1 Pscd1 4.69 BE113233 Suppressor of cytokine signaling 2 Socs2 4.68 NM_053949 Potassium voltage-gated channel, subfamily H (eag- Kcnh2 4.60 related), member 2 NM_017305 Glutamate cysteine ligase, modifier subunit Gclm 4.59 NM_017309 Protein phospatase 3, regulatory subunit B, alpha Ppp3r1 4.54 isoform,type 1 NM_012765 5-hydroxytryptamine (serotonin) receptor 2C Htr2c 4.46 NM_017218 V-erb-b2 erythroblastic leukemia viral oncogene homolog Erbb3 4.42 3 (avian) AW918369 Zinc finger protein 191 Zfp191 4.38 NM_031034 Guanine nucleotide binding protein, alpha 12 Gna12 4.38 NM_017020 Interleukin 6 receptor Il6r 4.37 AJ002942
    [Show full text]
  • Allelic Deletions on Chromosome 11Q13 in Multiple Endocrine Neoplasia Type 1- Associated and Sporadic Gastrinomas and Pancreatic Endocrine Tumors
    ICANCERRESEARCH57.2238—2243.June1. 19971 Allelic Deletions on Chromosome 11q13 in Multiple Endocrine Neoplasia Type 1- associated and Sporadic Gastrinomas and Pancreatic Endocrine Tumors Larisa V. Debelenko, Zhengping Zhuang, Michael R. Emmert-Buck, Settara C. Chandrasekharappa, Pachiappan Manickam, Siradanahalli C. Guru, Stephen J. Marx, Monica C. Skarulis, Allen M. Spiegel, Francis S. Collins, Robert T. Jensen, Lance A. Liotta, and Irma A. Lubensky' Laboratory of Pathology, National Cancer institute IL V. D., 1 1, M. R. E-B., L A. L, i. A. LI, National Centerfor Human Genome Research [S. C. C., P. M., S. C. G., F. S. C.], and Branches of Metabolic Diseases (S. J. M., A. M. S.], Diabetes [M. C. S.), and Digestive Diseases [R. T. ii, National Institute of Diabetes and Digestive and Kidney Diseases, N/H. Bethesda, Maryland 20892 ABSTRACT MEN] is a tumor suppressor gene (9—11).MEN1 patients are hypoth esized to inherit a mutation in one copy of the gene, and susceptible Endocrine tumors (ETs) of pancreas and duodenum occur sporadically cells in the target organs are transformed through the inactivation of and as a part of multiple endocrine neoplasia type 1 (MEN1). The MENJ the wild-type copy of the gene, potentially occurring via point muta tumor suppressor gene has been localized to chromosome 11q13 by link age analysis but has not yet isolated. Previous alleic deletion studies in tions, deletions, or gene methylation (6, 7, 10, 11). Sporadic parathy enteropancreatic ETs suggested MENJ gene involvement in tumorigenesis roid and enteropancreatic ETs have also been described to exhibit of familial pancreatic ETs (nongastrinomas) and sporadic gastrinomas.
    [Show full text]
  • Inflammation Leads to Distinct Populations of Extracellular Vesicles from Microglia Yiyi Yang1* , Antonio Boza-Serrano1, Christopher J
    Yang et al. Journal of Neuroinflammation (2018) 15:168 https://doi.org/10.1186/s12974-018-1204-7 RESEARCH Open Access Inflammation leads to distinct populations of extracellular vesicles from microglia Yiyi Yang1* , Antonio Boza-Serrano1, Christopher J. R. Dunning2, Bettina Hjelm Clausen3,4, Kate Lykke Lambertsen3,4,5 and Tomas Deierborg1* Abstract Background: Activated microglia play an essential role in inflammatory responses elicited in the central nervous system (CNS). Microglia-derived extracellular vesicles (EVs) are suggested to be involved in propagation of inflammatory signals and in the modulation of cell-to-cell communication. However, there is a lack of knowledge on the regulation of EVs and how this in turn facilitates the communication between cells in the brain. Here, we characterized microglial EVs under inflammatory conditions and investigated the effects of inflammation on the EV size, quantity, and protein content. Methods: We have utilized western blot, nanoparticle tracking analysis (NTA), and mass spectrometry to characterize EVs and examine the alterations of secreted EVs from a microglial cell line (BV2) following lipopolysaccharide (LPS) and tumor necrosis factor (TNF) inhibitor (etanercept) treatments, or either alone. The inflammatory responses were measured with multiplex cytokine ELISA and western blot. We also subjected TNF knockout mice to experimental stroke (permanent middle cerebral artery occlusion) and validated the effect of TNF inhibition on EV release. Results: Our analysis of EVs originating from activated BV2 microglia revealed a significant increase in the intravesicular levels of TNF and interleukin (IL)-6. We also observed that the number of EVs released was reduced both in vitro and in vivo when inflammation was inhibited via the TNF pathway.
    [Show full text]